Summary

This protein belongs to a complex called OST (oligosaccharyltransferase), which transfer the precursor N-glycan to a newly translated protein on its target sequence (usually a Asn-X-Ser/Thr motif, or a Asn-X-Cys)

Summary (from Uniprot)

Disease relevance of DAD1

• Enhanced expression of mRNAs of antisecretory factor-1, gp96, DAD1 and CDC34 in human hepatocellular carcinomas [1].
• Eutopic but not ectopic ECs also expressed increased TA of the antiapoptotic DAD-1 gene in endometriosis [2].
• Furthermore, expression of the anti-apoptotic tumor necrosis factor receptor associated factor 1 (TRAF1) and defender-against cell death (DAD-1) is regulated by NF-kappaB in certain breast cancer cells [3].
• A cDNA of a processed gene of human DAD-1 (defender against apoptotic cell death) was cloned from the human neuroblastoma cell line SH-SY5Y [4].

High impact information on DAD1

• Two independently derived Daudi x Hela D98 (male x female) hybrids, DAD 1 and DAD 10, demonstrated even higher H-Y antigen levels comparable to that of normal male peripheral blood lymphocytes [5].
• Here we use a GFP-tagged subunit of the OST complex (GFP-Dad1) that rescues the temperature-sensitive (ts) phenotype of tsBN7 cells, where Dad1 is degraded and N-glycosylation is inhibited, to study the lateral mobility of the TC by FRAP [6].
• Overexpression of Dad1/PhCCD8 in the dad1-1 mutant complemented the mutant phenotype, and RNA interference in the wild type resulted in an increased branching phenotype [7].
• Other differences in phenotype associated with the loss of Dad1/PhCCD8 function included altered timing of axillary meristem development, delayed leaf senescence, smaller flowers, reduced internode length, and reduced root growth [7].
• DAD1, the defender against apoptotic cell death, is a subunit of the mammalian oligosaccharyltransferase [8].

Biological context of DAD1

• The demonstration that DAD1 is a subunit of the OST suggests that induction of a cell death pathway upon loss of DAD1 in the tsBN7 cell line reflects the essential nature of N-linked glycosylation in eukaryotes [8].
• The DAD1 protein, whose defect causes apoptotic cell death, maps to human chromosome 14 [9].
• The highly conserved defender against the death 1 (DAD1) gene maps to human chromosome 14q11-q12 and mouse chromosome 14 and has plant and nematode homologs [10].
• We propose that HS2-6 primarily functions as an insulator or boundary element that may be critical for the autonomous regulation of the TCR alpha and Dad1 genes [11].
• A point mutation in the DAD1 gene is responsible for the temperature-sensitive phenotype of a baby hamster kidney-derived cell line (tsBN7) that undergoes apoptosis at the non-permissive temperature [12].

Anatomical context of DAD1

• DAD1, the defender against apoptotic cell death, was initially identified as a negative regulator of programmed cell death in the BHK21-derived tsBN7 cell line [8].
• DAD1 can be crosslinked to OST48 in intact microsomes with dithiobis(succinimidylpropionate) [8].
• Consistently, DAD1 binds well to Mcl-1 in COS cells when overexpressed [13].
• Statistical assessment of differential expression (significance analysis of microarrays) revealed upregulated transcripts for growth factors [heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), fibroblast growth factor (FGF), interleukin (IL)-6] and downregulated transcripts for genes that inhibit growth (BAX, p27KIP1, DAD1) [14].
• This work presents evidence that bilateral microinjection of the DAD1 agonist SKF-38393 into the substantia nigra enhances the susceptibility of rats to seizures, with an ED50 of 20 pmol (range 13-31 pmol), converting subconvulsant doses of the cholinergic agonist pilocarpine (200 mg/kg; i.p.) into convulsant ones [15].

Associations of DAD1 with chemical compounds

• A tomato lipase homologous to DAD1 (LeLID1) is induced in post-germinative growing stage and encodes a triacylglycerol lipase [16].
• Both methods showed that tunicamycin induces apoptosis in wild-type BHK21 cells, similar to the defect of Dad1p [17].
• * Background and Aims Evidence from pea rms1, Arabidopsis max4 and petunia dad1 mutant studies suggest an unidentified carotenoid-derived/plastid-produced branching inhibitor which moves acropetally from the roots to the shoots and interacts with auxin in the control of apical dominance [18].

Other interactions of DAD1

• On the other hand, DAD1 and interleukin-1 beta-converting enzyme (ICE) were downregulated while bcl-xs and Ich-1s were upregulated [19].
• Evaluation of antiapoptotic gene transcripts shows an upregulation in the expression of cFLIP, Bcl-2, Bcl-xL, DAD1 and survivin [20].
• In addition to the defender against death cell 1 (DAD1) gene, overexpressed clones corresponded mostly to expressed sequence tags (ESTs) [21].
• DAD-R has several possible initiation codons, one of them producing an open reading frame comprising 75% of the DAD-1 gene [4].
• In our earlier studies, we have demonstrated that CLL cells have differential expression of genes that are associated with apoptosis and cell cycle regulation, including elevated expression of Bcl-2, DAD-1, Cyclin D3 and cyclin dependent kinase 4 inhibitor [22].

Analytical, diagnostic and therapeutic context of DAD1

• Molecular cloning of a human cDNA encoding a novel protein, DAD1, whose defect causes apoptotic cell death in hamster BHK21 cells [23].
• By means of a two-hybrid method involving DAD1 as bait, the C-terminal region of Mcl-1, one of the bcl-2 family, was isolated [13].
• We also confirmed grade-associated levels of defender against death (DAD1) protein and HSD17 beta4 transcripts by immunohistochemistry and quantitative RT-PCR, respectively [24].
• Sequence analysis of the cDNA encoding the DAD1 homologue of A. ventricosus revealed that the 339-bp cDNA has an open reading frame of 113 amino acid residues [25].
• Northern blot analysis shows that the transcripts of A. ventricosus DAD1 homologue gene are present in all tissues examined, suggesting that A. ventricosus DAD1 is expressed in most, if not all, body tissues [25].

References